The antiinflammatory properties of ivermectin and brimonidine in the treatment of papulopustular rosacea
J Am Acad Dermatol
Introduction: The pathophysiology of papulopustular rosacea (PPR) is not fully understood; however, there is increasing evidence that immune and inflammatory responses play an important role in the persistent and perilesional erythema of PPR. Multiple trials have demonstrated the efficacy of ivermectin 1% cream (IVM) and brimonidine 0.33% gel (BR) for treatment of the inflammatory lesions and erythema of PPR, respectively. Two recent studies suggest a promising synergy between IVM and BR in PPR.
Methods: In mice, ear edema was induced via topical TPA 0.01%, followed by topical vehicle, IVM (0.1% to 1%), or BR 0.2%. Ear thickness (μm) was measured using a micrometer. In human subjects, in a multicenter, randomized, double-blind, vehicle-controlled study of moderate/severe rosacea (Investigator Global Assessment [IGA] ≥3) patients were treated with once-daily: 1. BR (morning) and IVM (evening), 12 weeks (IVM+BR/12W; n = 49); 2. BR vehicle and IVM, 4 weeks, followed by BR and IVM, 8 weeks (IVM+BR/8W; n = 46); 3. BR vehicle and IVM vehicle, 12 weeks (n = 95). Assessments included IGA (0-4), Clinician’s Erythema Assessment (CEA; 0-4), and inflammatory lesion count. Adverse events (AEs) were monitored throughout the study.
Results: In the mouse, IVM treatment inhibited TPA induced skin inflammation in a dose dependent manner, and combination treatment using topical IVM and BR further reduced ear edema. Clinically, IVM+BR showed superior efficacy in all subgroups, with the greatest efficacy seen in the IVM+BR/12W group vs. vehicle (IGA success [clear/almost clear], 61.2% vs. 36.8%; P = .003). Eight treatment-related AEs in 6 subjects (3.2%) were reported (including treatment-related worsening of rosacea: 1 with IVM+BR [subject 8090-116], 3 with vehicle).
Summary: Adding BR to IVM treatment reduced inflammation in vivo, and demonstrated good efficacy and safety clinically. This treatment combination may improve treatment success without impairing tolerability.